Lerkamen 20, pills 20mg, 60pcs

Composition

Active ingredients:  

lercanidipine hydrochloride 20 mg.

Auxiliary substances:  

lactose monohydrate – 60 mg,

microcrystalline cellulose-78 mg,

sodium carboxymethyl starch (type A) – 31 mg,

povidone K 30-9 mg,

magnesium stearate-2 mg.

Shell composition:

opadray 02F25077 – 6 mg (hypromellose-3,825 mg, talc-0.3 mg, titanium dioxide-1.2 mg, macrogol 6000-0.6 mg, iron oxide (III) – 0.075 mg).

Pharmacological action

Pharmacodynamics

Selective blocker of slow calcium channels with a predominant effect on blood vessels, dihydropyridine derivative. Inhibits the transmembrane flow of calcium ions into vascular smooth muscle cells. The mechanism of antihypertensive action of lercanidipine is due to a direct relaxing effect on vascular smooth muscle cells, resulting in a decrease in OPSS.

Despite the relatively short plasma half-life, lercanidipine has a prolonged antihypertensive effect due to its high membrane distribution coefficient. Due to its high vascular selectivity, it does not have a negative inotropic effect. Acute arterial hypotension with reflex tachycardia is rare due to the gradual development of vasodilation when taking lercanidipine.

Lercanidipine is a racemic mixture of (+)R – and (-)S-enantiomers. The antihypertensive effect of lercanidipine is primarily due to the S-enantiomer.

The duration of therapeutic action is 24 hours

. Pharmacokinetics

Suction

Lercanidipine is completely absorbed after oral use. Cmax in blood plasma is reached in 1.5-3 hours and is 3.3±2.09 ng / ml and 7.66±5.90 ng / ml after taking 10 and 20 mg of lercanidipine, respectively.

The (+) R-and (-) S-enantiomers of lercanidipine show a similar pharmacokinetic profile: they have the same time to reach Cmax, the same T1 / 2; the Cmax and AUC values are 1.2 times higher for the (-)S-enantiomer. No interconversion of enantiomers was observed in in vivo experiments.

Due to the” first pass ” effect through the liver, the absolute bioavailability of lercanidipine when taken orally after a meal is approximately 10%, when taken on an empty stomach, the bioavailability value decreases by 1/3. When taking lercanidipine no later than 2 hours after taking a fatty meal, its bioavailability increases 4-fold, so Lerkamen® should not be taken after a meal. When lercanidipine is administered orally, its plasma concentration is not directly proportional to the dose taken (nonlinear kinetics). Saturation of presystemic metabolism occurs gradually. Thus, bioavailability increases with increasing dose.

Distribution

Distribution from blood plasma to tissues and organs is rapid and extensive. Binding to plasma proteins exceeds 98%.

Metabolism and elimination

Lercanidipine is metabolized by the CYP3A4 isoenzyme to form inactive metabolites.

About 50% of the dose taken is excreted by the kidneys (about 50% is excreted by the intestines). Elimination occurs mainly by biotransformation. The average T1 / 2 is 8-10 hours.

Accumulation of lercanidipine with repeated oral use is not observed.

Pharmacokinetics in special clinical cases

The pharmacokinetics of lercanidipine in elderly patients, patients with renal insufficiency (creatinine clearance greater than 30 ml/min), and patients with mild to moderate hepatic insufficiency have been shown to be similar to those observed in the general patient population.

In patients with renal insufficiency (creatinine clearance less than 30 ml/min) and in patients undergoing hemodialysis, lercanidipine plasma concentrations were higher (approximately 70%).

In patients with severe renal and/or hepatic insufficiency, the free fraction of lercanidipine may increase due to a decrease in the concentration of protein in the blood plasma.

In patients with moderate to severe hepatic insufficiency, the systemic bioavailability of lercanidipine is likely to increase, since lercanidipine is mainly metabolized in the liver.

Indications

Essential hypertension of I-II degrees of severity.

Use during pregnancy and lactation

The use of Lerkamen® during pregnancy and lactation, as well as in women of childbearing age in the absence of reliable contraception is contraindicated.

Preclinical studies did not reveal the teratogenic effect of lercanidipine in rats and rabbits, and the reproductive function of rats was unchanged.

Due to the lack of clinical experience with the use of lercanidipine during pregnancy and lactation, and since it is known that other dihydropyridine derivatives have had a teratogenic effect in animals, lercanidipine is not recommended for use during pregnancy and in women of childbearing age who do not use reliable methods of contraception.

Due to the high lipophilicity of lercanidipine, its penetration into breast milk can be assumed, so the drug is not recommended for use during breastfeeding.

Contraindications

• Hypersensitivity to other derivatives digidropiridinovmi range;
• untreated heart failure;
• unstable angina;
• obstruction of blood vessels originating from the left ventricle of the heart;
• period within 1 month after myocardial infarction;
• severe hepatic impairment;
• renal failure severe (CC less than 30 ml/min);
• concomitant use with CYP3A4 inhibitors (ketoconazole, Itraconazole, erythromycin, ritonavir, troleandomycin);
• simultaneous use with cyclosporine;
• simultaneous reception with grapefruit juice;
• lactose intolerance, lactase deficiency, the syndrome of glucose-galactose malabsorption;
• pregnancy and lactation (breastfeeding);
• use in women of childbearing age not using reliable methods of contraception;
• childhood and adolescence to 18 years (effectiveness and safety have not been studied);
• hypersensitivity to the components of the drug.

With caution: it should be used: with renal (creatinine clearance more than 30 ml/min) and/or hepatic insufficiency of mild to moderate severity, in elderly patients, with SSS (without pacemaker), coronary heart disease, left ventricular dysfunction.

Side effects

Possible side effects are listed below by descending frequency of occurrence:

• common ( < 1/10, ≥1/100);
• uncommon ( < 1/100, ≥1/1000);
• rare ( < 1/1000, ≥1/10000);
• very rare (

From the nervous system: infrequently-headache, dizziness; rarely-drowsiness.

From the cardiovascular system: infrequently-palpitation, tachycardia, “flushes” of blood to the skin of the face; rarely-angina pectoris, pain behind the sternum; very rarely-fainting, in patients with angina, an increase in the frequency, duration and severity of attacks is possible.

From the digestive system: rarely-nausea, dyspepsia, diarrhea, epigastric pain, vomiting.

Skin and subcutaneous tissue disorders: rarely – skin rash.

Musculoskeletal disorders: rarely-myalgia.

From the urinary system: rarely-polyuria.

Immune system disorders: very rare – hypersensitivity reactions.

From the body as a whole: infrequently – peripheral edema; rarely – asthenia, increased fatigue.

The following very rare side effects have been reported (

Interaction

Lercanidipine can be used simultaneously with beta-blockers, diuretics, and ACE inhibitors.

When co-administered with metoprolol, the bioavailability of lercanidipine decreases by 50%. This effect may also occur when used concomitantly with other beta-blockers, so it may be necessary to adjust the dose of lercanidipine to achieve a therapeutic effect with this combination.

Lercanidipine is metabolized with the participation of the CYP3A4 isoenzyme, so inhibitors and inducers of this isoenzyme, when used simultaneously, can affect the metabolism and excretion of lercanidipine. Concomitant use of lercanidipine with CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) is not recommended.

Concomitant use of cyclosporine and lercanidipine is not recommended, as there is an increase in the concentration of both substances in the blood plasma.

Caution should be exercised when lercanidipine is co-administered with other CYP3A4 substrates (terfenadine, astemizole, Class III antiarrhythmic drugs, such as amiodarone, quinidine).

When lercanidipine 20 mg is co-administered with midazolam, the bioavailability of lercanidipine in elderly patients may increase by approximately 40%.

Lercanidipine should be administered with caution simultaneously with inducers of CYP3A4, for example, anticonvulsants (phenytoin, carbamazepine) and rifampicin, since the antihypertensive effect of the drug may decrease. Regular blood pressure monitoring is required.

No pharmacokinetic interaction was observed with concomitant use of lercanidipine at a dose of 20 mg in patients who were constantly taking beta-methyldigoxine, while in healthy volunteers treated with digoxin, the Cmax value for digoxin increased by an average of 33% after taking 20 mg of lercanidipine on an empty stomach, while AUC and renal clearance changed slightly. It is necessary to monitor the presence of signs of digoxin intoxication in patients taking digoxin and lercanidipine simultaneously.

Concomitant use of lercanidipine with cimetidine (up to 800 mg) does not cause significant changes in the concentration of lercanidipine in blood plasma. At high doses of cimetidine, the bioavailability and antihypertensive effect of lercanidipine may increase.

When lercanidipine (20 mg) and simvastatin (40 mg) were co – administered, the AUC value for simvastatin increased by 56%, and the same value for its active metabolite-beta-hydroxy acid-by 28%. When taking medications at different times of the day (lercanidipine in the morning, simvastatin in the evening), undesirable interactions can be avoided.

No changes in the pharmacokinetics of warfarin were observed when lercanidipine 20 mg was co-administered with warfarin in healthy volunteers.

Concomitant use with fluoxetine (a CYP2D6 and CYP3A4 inhibitor) in elderly patients did not have clinically significant changes in the pharmacokinetics of lercanidipine.

It is possible to increase the antihypertensive effect when taking grapefruit juice and lercanidipine at the same time.

Ethanol may potentiate the antihypertensive effect of lercanidipine.

How to take, course of use and dosage

The drug is taken orally, at least 15 minutes before meals, preferably in the morning, without chewing, with a sufficient amount of water.

Assign 10 mg 1 time / day. Depending on the individual tolerance of the drug to the patient, the dose can be increased to 20 mg.

The therapeutic dose is selected gradually, since the maximum antihypertensive effect develops approximately 2 weeks after the start of taking the drug. It is unlikely that the effectiveness of the drug will increase with an increase in the dose of more than 20 mg / day, at the same time, the risk of side effects increases.

The pharmacokinetic profile and data from clinical studies indicate that no dose adjustment of Lerkamen is required in elderly patients. However, caution should be exercised at the initial stage of treatment with Lerkamen® in this group of patients.

Caution should be exercised when using Lerkamen in patients with mild to moderate renal and hepatic insufficiency.

In case of renal insufficiency (creatinine clearance more than 30 ml / min) or mild or moderate hepatic insufficiency, the initial dose is 10 mg, then the dose is increased with caution to 20 mg / day.

The antihypertensive effect may be increased in patients with mild or moderate hepatic insufficiency and dose adjustment (reduction) may be required.

In patients with renal insufficiency (creatinine clearance less than 30 ml / min) and severe hepatic insufficiency, the use of Lerkamen® is contraindicated.

Overdose

Presumably, in the case of an overdose of lercanidipine, symptoms similar to those of an overdose of other dihydropyridine derivatives will be observed: peripheral vasodilation with a pronounced decrease in blood pressure and reflex tachycardia.

Treatment: symptomatic therapy; in the case of a marked decrease in blood pressure, loss of consciousness, cardiovascular therapy is indicated, with bradycardia – intravenous use of atropine.

There are data on 3 cases of overdose when taking lercanidipine in doses of 150 mg,280 mg and 800 mg for the purpose of suicide.

In the case of taking 150 mg of lercanidipine + alcohol (unknown amount), drowsiness was observed.

Treatment: gastric lavage, taking activated charcoal.

When taking 280 mg of lercanidipine + 5.6 mg of moxonidine, the following symptoms were observed: cardiogenic shock, severe myocardial ischemia, mild renal failure.

Treatment: cardiac glycosides, diuretics (furosemide), high-dose catecholamines, plasma substitutes. In the case of taking 800 mg of lercanidipine, nausea and a marked decrease in blood pressure were observed.

Treatment: taking activated charcoal and laxatives, IV-dopamine.

In all cases of overdose, all patients remained alive. There is no information on the effectiveness of dialysis for lercanidipine. It is most likely that due to the high binding of lercanidipine to plasma proteins, dialysis may not be effective.

Special instructions

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Since dizziness, asthenia, fatigue and, in rare cases, drowsiness may occur during therapy with Lerkamen®, patients should drive vehicles with extreme caution and engage in other potentially dangerous activities that require a high rate of psychomotor reactions.

Form of production

Film-coated tablets.

Storage conditions

Keep out of reach of children at a temperature not exceeding 30°C.

Shelf

life is 3 years.

Active ingredient

Lercanidipine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets